The percutaneous injection of substances into tissues to augment, support, or reconfigure anatomic structure has been the subject of significant research and development and is well known in the art. See, for example, U.S. Pat. Nos. 4,803,075 and 5,204,382 to Wallace et al., and U.S. Pat. No. 5,258,028 to Ersek et al. Procedures have been described in the medical literature for correction of dermatological, otolaryngological problems and for treatment of urological disorders, e.g., Smith et al., "Evaluation of Polydimethylsiloxane as an Alternative in the Endoscopic Treatment of Vesicoureteral Reflux", J. Urol., 152: 1221-1224, 1994, and Walker et al., "Injectable Bioglass as a Potential Substitute for Injectable: Polytetrafluorethylene", J Urol., 148:645-7 (1992) and the references cited therein.
Urinary incontinence and vesicourethral reflux are urological disorders that have responded to treatments with augmentative materials. Incontinence occurs when the resistance to urine flow has decreased to the point where the resistance can no longer resist the intra-abdominal pressure. Nearly all procedures developed to restore continence are based on restoring the lost resistance to urine outflow. U.S. Pat. Nos. 5,007,940; 5,158,573; and 5,116,387 to Berg disclose biocompatible compositions comprising discrete, polymeric and silicone rubber bodies injectable into urethral tissue for the purpose of treatment of urinary incontinence by tissue bulking. Further, U.S. Pat. No. 5,452,406 to Lawin discloses biocompatible compositions comprising carbon coated substrate particles injectable into a tissue, such as the tissues of and that overlay the urethra and bladder neck, for the purpose of treatment of urinary incontinence by tissue bulking.
The most serious adverse effects that may occur from therapies of this type relate to the migration of the solid materials from the original site of placement into repository sites in various body organs and the chronic inflammatory response of tissue to particles that are too small. These adverse effects are well documented in the urologic literature, specifically in Malizia, A. A. et al., "Migration and Granulomatous Reaction After Periurethral Injection of Polytef (Teflon)", JAMA 251:3277-3281 (1984) and Claes, H., Stroobants, D. et al., "Pulmonary Migration Following Periurethral Polytetrafluoroethylene Injection For Urinary Incontinence", J. Urol., 142:821-822 (1989). An important factor in assuring the absence of migration is the administration of properly sized particles. If the particle is too small, it can be engulfed by the body's white cells (phogocytes) and carried to distant organs or be carried away in the microvasculature and travel until it reaches a site of greater constriction. Target organs for deposition include the lungs, liver, spleen, brain, kidney, and lymph nodes.
The use of small diameter particulate spheres, in the range of 1-20 microns, formed of materials such as cross linked collagen or synthetic polymers suspended in an aqueous medium having biocompatible lubricant has been disclosed in Wallace et al., U.S. Pat. No. 4,803,075. While these materials showed positive, short term augmentation results, this result was short lived as the material had a tendency to migrate and/or be absorbed by the host tissue. Teflon paste was used early to treat stress urinary incontinence. Politano, V. S., Small, M. P., Harper, J. M., Lynne, C. M., "Periurethral Teflon Injection for Urinary Incontinence", J. Urol., 111:180-183 (1974). The Teflon paste consisted of Polytetrafluoroethylene particles in a size range of 1 to 100 microns. More than ninety percent of the particles were in the range of 1 to 40 microns. Malizia, A. A. Reiman, H. M., Myers, R. P. et al. , "Migration and Granulomatous Reaction After Periurethral Injection of Polytef (Teflon)", JAMA, 251:24:3277-3281 (1984). This product demonstrated foreign body granuloma formation at the injection site and local migration. Boedts, D., Roels, H., Kluyskens, P., "Laryngeal Tissue Responses to Teflon", Arch Otolarynqol, 86:562-567 (1967).
Proper particle size selection is important. Studies indicate that a particle size for Teflon (PTFE) in the range of between 1 and 100 microns is unacceptable for injectable material. Particles in this size range show local and distant migration, produce chronic inflammatory responses in tissue, and has been associated with clinical complications. Particles that are too large are difficult to deposit e.g. will not go down a needle small enough to have clinical application.
U.S. Pat. No. 5,792,478 to Lawin, issued Aug. 11, 1998, assigned to the assignee of the present invention, discusses pure carbon beads (either graphite or pyrolytic carbon substrate material) which is coated with pyrolytic carbon to form a pure carbon bead and a B-glucan carrier gel.
The primary focus of the present invention has been directed toward the development of improved biocompatible, nonmigratory particles that are effectively delivered to the desired tissue site in an improved lubricative, biocompatible fluid or gel carrier. The preferred carrier shall not cause any deleterious effects from the site by normal biological or biochemical processes such as excretion or metabolic breakdown.